Randomized phase II trial of farletuzumab plus chemotherapy versus placebo plus chemotherapy in low CA-125 platinum-sensitive ovarian cancer.

The primary purpose of this study was to determine if farletuzumab, an antifolate receptor-α monoclonal antibody, improved progression-free survival (PFS) versus placebo when added to standard chemotherapy regimens in patients with platinum-sensitive recurrent ovarian cancer (OC) in first relapse (platinum-free interval: 6-36 months) with low cancer antigen 125 (CA-125) levels. Eligibility included CA-125 ≤ 3 x upper limit of normal (ULN, 105 U/mL), high-grade serous, platinum-sensitive recurrent OC, previous treatment with debulking surgery, and first-line platinum-based chemotherapy with 1st recurrence between 6 and 36 months since frontline platinum-based treatment. Patients received investigator's choice of either carboplatin (CARBO)/paclitaxel (PTX) every 3 weeks or CARBO/pegylated liposomal doxorubicin (PLD) every 4 weeks x6 cycles in combination with either farletuzumab [5 mg/kg weekly] or placebo randomized in a 2:1 ratio. Maintenance treatment with farletuzumab (5 mg/kg weekly) or placebo was given until disease progression or intolerance. 214 patients were randomly assigned to farletuzumab+chemotherapy (142 patients) versus placebo+chemotherapy (72 patients). The primary efficacy endpoint, PFS, was not significantly different between treatment groups (1-sided α = 0.10; p-value = 0.25; hazard ratio [HR] = 0.89, 80% confidence interval [CI]: 0.71, 1.11), a median of 11.7 months (95% CI: 10.2, 13.6) versus 10.8 months (95% CI: 9.5, 13.2) for farletuzumab+chemotherapy and placebo+chemotherapy, respectively. No new safety concerns were identified with the combination of farletuzumab+chemotherapy. Adding farletuzumab to standard chemotherapy does not improve PFS in patients with OC who were platinum-sensitive in first relapse with low CA-125 levels. Folate receptor-α expression was not measured in this study. (Clinical Trial Registry NCT02289950).

Informations de copyright

Copyright © 2023. Published by Elsevier Inc.

Déclaration de conflit d'intérêts

Declaration of Competing Interest TH reports medical writing support; consulting fees from Astra Zeneca (AZ), Caris, Clovis, Genentech, Gradalis, Epsilogen, Merck (MSD), Eisai, Seagen; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AZ, Clovis, GlaxoSmithKline (GSK); participation on a Data Safety Monitoring Board or Advisory Board from Incyte, Corcept; Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid as Treasurer GOG Foundation and Associate Director GOG-P. SP reports no conflicts of interest. SG reports payments for clinical trial conduct from Eisai; grants or contracts for clinical trial conduct from GSK, Merck, Mersana, Jounce, AZ, Seagen, Clovis; consulting fees from Seagen; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Eisai and GSK; Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid as GOG foundation, GASCO, National Cancer Institute Cervix committee. MR reports no conflicts of interest. KF reports grants and contracts from Eisai; consulting fees from Eisai. CV reports medical writing support from Eisai; consulting fees from Janssen-Cilag, Roche, GSK, Atheneum Partners, Astellas Pharma, MSD, Bristol Myers Squibb (BMS), Leo-Pharma; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Janssens Cilag, Leo Pharma, Bayer; support for attending meetings and/or travel from Roche and Pfizer. DA reports clinical trial support from Eisai. JS reports consulting fees from Eisai, Roche, Novocure, AZ, GSK, Tesaro, Pfizer, MSD, Merck, Clovis; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Eisai, Roche, Novocure, AZ, GSK, Tesaro, Pfizer, MSD, Merck; payment for expert testimony from Eisai, Roche, Novocure, AZ, GSK, Tesaro, Pfizer, MSD, Merck; support for attending meetings and/or travel from GSK, Roche, AZ; participation on a Data Safety Monitoring Board or Advisory Board from Eisai, Roche, Novocure, AZ, GSK, Tesaro, Pfizer, MSD, Merck, Clovis; Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid as ESGO council, NOGGO council, AGO Executive Board, GCIG member; RC reports grants or contracts from AZ, Clovis, Genelux, Genmab, Merck, Immunogen Janssen, Roche/Genentech; consulting fees from Agenus, Alkermes, AZ, Clovis, Deciphera, Genelux, Genmab, GSK, Immunogen, Janssen, OncoQuest, Onxeo, Onxerna, Regeneron, Roche/Genentech, Novocure, Merck, Abbvie; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AZ, Clovis, Roche/Genentech, Merck; participation on a Data Safety Monitoring Board or Advisory Board from VBL Therapeutics. HG reports no conflicts of interest. GS reports grants or contracts from MSD Italia; consulting fees from Tesaro Bio Italy srl, Johnson and Johnson; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Clovis Oncology Italy srl. BM reports consulting fees from Acrivon, Adaptimune, Agenus, Akeso Bio, Amgen, Aravive, AZ, Bayer, Clovis, Eisai, Elevar, EMD Merck, Genmab/Seagen, GOG Foundation, Gradalis, Heng Rui, ImmunoGen, Karyopharm, Lovance, Laekna, Macrogenics, Merck, Mersana, Myriad, Novartis, Novocure, OncoC4, Panavance, Pieris, Pfizer, Puma, Regeneron, Roche/Genentech, Sorrento, Tesaro/GSK, US Oncology Research, VBL, Verastem, Zentalis; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AZ, Clovis, Eisai, Merck, Myriad, Roche/Genentech, Tesaro/GSK. JA reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from BMS, Merck, Astellas, Eisai, Ipsen, Pfizer; support for attending meetngs and/or travel from Ipsen. KU reports grants or contracts from Eisai. RH reports grants or contracts from AZ, Clovis, GSK; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AZ, Clovis, GSK; multiple cases for medicolegal expert witness; participation on a Data Safety Monitoring Board or Advisory Board from AZ, Clovis, GSK. CZ reports grants or contracts from Novartis; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Roche, Novartis, Pfizer, Lilly, AstraZeneca, MSD, Eisai, GSK; support for attending meetings or travel from Roche, Novartis, Pfizer, Lilly, AstraZeneca, MSD, Eisai, GSK, ExactSciences, Clovis; participation on a Data Safety Monitoring Board or Advisory Board from Roche, Novartis, Pfizer, Lilly, AstraZeneca, MSD, Eisai, GSK, DaichiSankyo. RW reports support for medical writing from Eisai; grants or contracts from OnTarget Labs, Merck, Anixa Bioscience; consulting fees from Novocure, Mersana, AZ, Ovation Diagnostics, Sonnet Biotherapeutics, Shattuck Labs, Clovis, Abbvie, Tesaro/GSK, Seagen, Genentech, Merck, Regeneron, Legend Biotech, Eisai; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AZ and GSK; support for attending meetngs and/or travel from Sonnet Biotherapeutics and Tapimmune; participation on a Data Safety Monitoring Board or Advisory Board from Tesaro, Seagen; stock or stock options from Ovation Diagnostics; AG reports grants or contracts from Roche and Tesaro/GSK; consulting fees from AZ, Genmab, MSD, Oncoinvent, PharmaMar, SOTIO, Clovis, Immunogen, Amgen Merck/Pfizer, Roche, GSK/Tesaro; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Roche, Tesaro/GSK, Clovis, Immunogen, Pfizer, Amgen, SOTIO, Marcrogenics, AZ, MSD, Genmab, Oncoinvent, EMD Serono, Mersana, SUTRO, PharmaMar; support for attending meetngs and/or travel from Roche, PharmaMar, AZ, Tesaro/GSK; BS reports consulting fees from AZ, Clovis, GSK, Merck, Eisai, Lilly, Novartis, Immunogen, Seagen, Genmab, Genentech; YJ reports employment from Eisai; LR reports employment from Eisai. KT reports support for the manuscript from Eisai; consulting fees from Merck, GSK, Clovis, AZ, Regeneron, Eisai, Seagen; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Merck, GSK, Clovis, AZ, Regeneron, Eisai, Seagen; participation on a Data Safety Monitoring Board or Advisory Board from Lovance. SW reports employment from Eisai. IV reports grants or contracts from Oncoinvent, AS, Amgen, Roche; consulting fees from Agenus, Akesobio, AZ BMS, Deciphera Pharmaceuticals, Eisai, Elevar Therapeutics, Exelixis, F. Hoffmann-La Roche, Genmab, GSK, Immunogen, Jazzpharma, Karyopharm, Mersana, MSD, Novocure, Novartis, Oncoinvent, OncXerna, Regeneron, Sanofi, Seagen, Sotio, Verastem Oncology, Zentalis; support for attending meetngs and/or travel from Karyopharm, Genmab, Novocure.